The pathological isoform of the prion protein (PrPres) can serve as a marker for prion diseases, but more practical tests are needed for preclinical diagnosis and sensitive detection of many prion infections. During FY2011, we 1) developed a new prion assay (called eQuIC) that allows for the ultrasensitive and rapid of prions in inhibitor-laden biological fluids such as blood plasma;2) adapted eQuIC to the detection of human, sheep, hamster and mouse prions in blood plasma samples;3) trained and collaborated with human TSE surveillance groups to evaluate the utility of our previously developed RT-QuIC assay for the diagnosis of human sporadic Creutzfeldt-Jakob disease;the data showed that when applied to clinical cerebral spinal fluid samples, RT-QuIC has better sensitivity and specificity than any prior diagnostic test.